The Twenty-Sixth International Eurotoxicology Conference (NEUROTOX 26) addressing the theme of "Unifying Mechanisms of Neurological Disorders" will be held June 6-11, 2010 in Portland, Oregon. The meeting location is the Portland Marriott Downtown Waterfront Hotel where greatly reduced conference rates have been negotiated. The International Neurotoxicology Conference is an annual event that focuses on a timely and provocative theme that has a high probability of advancing the field by being addressed by an interdisciplinary, international group of scientists in the unique "atmosphere" and organized format of this established Conference Series - while at the same time providing an opportunity for presenting new data related to the general interdisciplinary field of neurotoxicology. The Specific Aims identified in the proposal will be accomplished by conducting a 4 day conference according to a varied format similar to previous conferences in this series which has proven to be highly successful. Each conference has its own "special touch" unique to the venue and consists of Tutorials, Symposia, Platform Sessions, -Workshops, Panel Discussions, Roundtables, Debates, Poster Session, Pre- and Postdoctoral Student Competition and Awards Banquet and social events as well as novel approaches to facilitate networking and mentoring. NEUROTOX 26 will not be simply an occasion to present data. It will also coalesce human, experimental animal, methodological, and epidemiological research by offering a well-recognized venue where previously unconnected investigators can come together and where commonalties can emerge. Traditionally the Neurotoxicology Conference places special emphasis on nurturing, promoting and rewarding pre- and post-doctoral students and young investigators. Extra effort is extended to mentor students and help them network with the leaders in the field. Justification for the Theme: Over the past several years, research into neurological disease and disorders has evolved to recognize that there are often overlapping similarities in seemingly different disease states. Although genetic factors have long been a primary focus in neurological disease, identification of single genes involved in more than a small fraction of cases in a variety of neurological disorders has proven difficult. These findings have led to the emerging recognition that environmental factors or gene-environment interactions are likely to play a pivotal role in disease pathogenesis. Thus, understanding common mechanisms and genetic and environmental factors that contribute to manifestation of neuronal dysfunction has the potential to provide insight into the pathophysiology of neurological disorders and ultimately lead to better prevention and treatment of disease. In order to accomplish the goal of understanding common mechanisms and contributors to neurological disease, we are proposing to convene a conference entitled "Unifying Mechanisms of Neurological Disorders". Through this conference, we plan to bring together experts in clinical medicine, basic science, toxicology, and translational research to explore common mechanisms of neurological disease with the goal of facilitating interactions and the transfer of knowledge between groups that have not historically interacted to a significant degree. We have chosen to focus on two major common mechanisms associated with a number of neurological disease states and three emerging areas of research that have the potential to benefit from increased focus. First, we will explore the role of mitochondrial dysfunction, which is a hallmark of several devastating neurological disease such as Parkinson's, Alzheimers, Huntington's, and ALS. The salient questions relating to mitochondrial function in disease to be assessed in this session will include the role of mitochondrial dysfunction in pathogenesis, the role of environmental factors and gene-environment interactions, and how mitochondrial function can be targeted for therapeutic intervention. The second major common mechanism of focus will be on the role of protein aggregation and misfolding in neurological disease. Protein aggregation and misfolding have been linked to a variety of neurological disorders, both genetic and idiopathic in origin. However, there is currently controversy as to whether this process is a cause or consequence of the disease process. This session will bring together experts in neuropathology, clinical medicine, and basic researchers to evaluate the role of protein aggregation and misfolding in neurological disease and what information relating to pathogenesis and treatment that can be gleaned from examining common mechanisms affecting these pathways. The three emerging areas that we have chosen for focus include channelopathies, gender, and epigentics. Channelopathies are thought to play an important role in epilepsy, chronic pain, and migraine. Although most of the focus has been on the role of genetic alterations in channel proteins, a variety of environmental toxicants target ion channels, which suggests the potential for environmental exposures to contribute to channelopathies. The IOM report, "Does Sex Matter" (2001) emphasized the need for examining differences between male and female responses in the research enterprise because of wide gaps between males and females in disease patterns and in response to therapeutic practices and drugs. This symposium is designed to exemplify both current knowledge of sex differences in environmenal chemical vulnerability and to propose insight into the relationship between the environmental exposures, gender, and the development of neurological disease. Finally, we will explore the role of epigenetic alterations in neurological disorders. Emerging evidence suggests that epigenetic alterations resulting from environmental exposures during critical periods of development may play a significant role in neurodevelopmental disorders. This session is designed to assess the current state of knowledge in this and identify common mechanisms involving epigenetic alterations that may provide insight into disease pathogenesis and ultimately, therapeutic intervention. PUBLIC HEALTH RELEVANCE: The health relatedness of this application is that he results of this conference will contribute to a fuller understanding of the true risk posed by exposure to a variety of neurotoxicants on human neurological diseases or disorders. Exposure to a variety of neurotoxicants has been associated with characteristic derangements of nervous system function, some fleeting in nature and others virtually permanent. Furthermore, exposure to neurotoxicants has been hypothesized to play a role in the development of many neurological diseases and disorders. NEUROTOXICOLOGY 26 will focus on common mechanisms in neurological disease and the role of environmental exposures and gene-environment interactions in the development of neurological disease and disorders.